gw-5074 and Skin-Neoplasms

gw-5074 has been researched along with Skin-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for gw-5074 and Skin-Neoplasms

ArticleYear
C-Raf is associated with disease progression and cell proliferation in a subset of melanomas.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2009, Sep-15, Volume: 15, Issue:18

    Raf-kinases include three major isoforms. Although the role of B-Raf in melanoma is well established, little is known about C-Raf. We studied effects of C-Raf knockdown in vitro and assessed expression of C-Raf in a large cohort of melanomas and nevi.. Using specific siRNAs, we knocked down C-Raf expression, and determined the effect on viability, MAP extracellular signal-regulated kinase (ERK)/ERK kinase signaling, and apoptosis in seven melanoma cell lines. We determined the IC(50) of the C-Raf inhibitors sorafenib and GW5074, and studied the effects of GW5074 on cell signaling. Using an automated method to measure in situ protein expression, we quantified C-Raf expression in 263 nevi and 523 melanomas.. C-Raf was knocked down in three cell lines with detectable phospho-C-Raf, resulting in decreased viability in two of the three (YULAC and YUROB). This resulted in decreased Bcl-2 expression and phospho-Bad cleavage, without affecting phospho-MEK and phospho-ERK. Sensitivity to sorafenib and GW5074 varied. GW5074 inhibited mitogen-activated protein kinase signaling without Bcl-2 and phospho-Bad down-regulation. C-Raf was highly expressed in melanomas compared with nevi (P < 0.0001), and no nevi had high C-Raf expression. C-Raf expression was higher in metastatic than primary specimens (P = 0.0225).. C-Raf siRNA knock-down results in decreased viability of YULAC (B-Raf(V600K)) and YUROB (B-Raf(WT)) melanoma cells, likely mediated by Bcl-2 inhibition rather than mitogen-activated protein kinase inhibition. Cotargeting C-Raf and parallel pathways might be an effective therapeutic approach for melanoma. C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cohort Studies; Disease Progression; Female; Gene Silencing; Humans; Indoles; Male; Melanoma; Middle Aged; Nevus; Niacinamide; Phenols; Phenylurea Compounds; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-raf; Pyridines; RNA, Small Interfering; Sensitivity and Specificity; Skin Neoplasms; Sorafenib; Young Adult

2009